Cannabis is the most abused substance among juvenile justice populations, with almost half (45%) of justice-involved adolescents meeting lifetime criteria for cannabis use disorders. However, only an estimated 26% achieve abstinence following psychosocial interventions. Biological risk factors are one understudied component that may influence the efficacy of psychosocial interventions. This proof of concept proposal seeks to apply a translational neurobiological model using functional MRI (fMRI) to evaluate the neural and genetic underpinnings of the initiation and maintenance of behavior change during and following a widely disseminated psychosocial intervention for adolescents with cannabis use disorders. Specifically, the first aim is to determine whether active ingredients signal a neurocognitive shift that underlies behavioral change (e.g., reduced cannabis use) following a psychosocial intervention. The second aim will explore whether genetic factors (dopamine receptor variants) may predict differential brain activation following receipt of a psychosocial intervention. To accomplish these aims, 64 marijuana-abusing adolescents (ages 14-17) will complete genetic, neurocognitive, and behavioral assessments at baseline and 6 weeks, and receive an empirically supported brief intervention for cannabis use disorders. The proposed research is expected to provide critical foundational data that will facilitate the development of translational studies investigating how and for whom psychosocial interventions work. PUBLIC HEALTH RELEVANCE: Cannabis is the most abused substance among juvenile justice populations, with almost half (45%) of justice-involved adolescents meeting lifetime criteria for cannabis use disorders. Unfortunately, only an estimated 26% of individuals achieve abstinence following psychosocial cannabis interventions. This proof of concept proposal seeks to innovatively integrate biological and behavioral approaches using functional MRI (fMRI) to evaluate the neural and genetic underpinnings of the initiation and maintenance of behavior change (reduced cannabis use) during and following a widely disseminated psychosocial intervention for adolescents with cannabis use disorders. To our knowledge, no one has explored whether functional brain differences mediate the impact of psychosocial addictions interventions. Integrating our understanding of brain activation and treatment response is likely to take a major step towards improving our understanding of patient response to psychosocial cannabis interventions.